Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Kinetic Isotope Effect in the Unfolding of a Protein Secondary Structure: Calculations for Beta-Sheet Polyglycine Dimers as a Model. / Яншин, Алексей Олегович; Kiselev, Vitaly; Бакланов, Алексей Васильевич.
в: Biomedicines, Том 15, № 1, 2561, 09.01.2025.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - Kinetic Isotope Effect in the Unfolding of a Protein Secondary Structure: Calculations for Beta-Sheet Polyglycine Dimers as a Model
AU - Яншин, Алексей Олегович
AU - Kiselev, Vitaly
AU - Бакланов, Алексей Васильевич
N1 - This research was funded by the Russian Science Foundation, grant number 23-23-00275.
PY - 2025/1/9
Y1 - 2025/1/9
N2 - In the present work, we performed calculations of the kinetic isotope effect (KIE) on H/D, 14N/15N, 16O/18O, and 12C/13C isotopic substitution in the dissociation of beta-sheet polyglycine dimers of different lengths into two monomer chains. This dissociation reaction, proceeding via breaking of the interchain hydrogen bonds (H-bonds), is considered to be a model of unfolding of the secondary structure of proteins. The calculated strengthening of the interchain hydrogen bonds 푁−퐻⋯푂=퐶 due to heavy isotope substitution decreases in the row H/D >> 14N/15N > 16O/18O > 12C/13C. The KIE for H/D substitution, defined as the ratio of the rate constants 푘(퐻)푘(퐷), was calculated with the use of a “completely loose” transition state model. The results of the calculations show that a very high H/D isotope effect can be achieved for proteins even with moderately long chains connected by dozens of interchain H-bonds. The results obtained also indicate that the heavy isotope substitution in the internal (interchain) and external H-bonds, located on the periphery of a dimer, can provide comparable effects on secondary structure stabilization.
AB - In the present work, we performed calculations of the kinetic isotope effect (KIE) on H/D, 14N/15N, 16O/18O, and 12C/13C isotopic substitution in the dissociation of beta-sheet polyglycine dimers of different lengths into two monomer chains. This dissociation reaction, proceeding via breaking of the interchain hydrogen bonds (H-bonds), is considered to be a model of unfolding of the secondary structure of proteins. The calculated strengthening of the interchain hydrogen bonds 푁−퐻⋯푂=퐶 due to heavy isotope substitution decreases in the row H/D >> 14N/15N > 16O/18O > 12C/13C. The KIE for H/D substitution, defined as the ratio of the rate constants 푘(퐻)푘(퐷), was calculated with the use of a “completely loose” transition state model. The results of the calculations show that a very high H/D isotope effect can be achieved for proteins even with moderately long chains connected by dozens of interchain H-bonds. The results obtained also indicate that the heavy isotope substitution in the internal (interchain) and external H-bonds, located on the periphery of a dimer, can provide comparable effects on secondary structure stabilization.
KW - brain metastases
KW - segmentation
KW - transfer learning
KW - completely loose transition state
KW - unfolding
KW - protein
KW - polyglycine dimer
KW - kinetic isotope effect
KW - hydrogen bond
KW - Protein Structure, Secondary
KW - Protein Unfolding
KW - Peptides/chemistry
KW - Protein Multimerization
KW - Models, Molecular
KW - Hydrogen Bonding
KW - Protein Conformation, beta-Strand
KW - Kinetics
KW - Dimerization
UR - https://www.mendeley.com/catalogue/da0d7a09-f8c4-38d3-9878-91aee60f51ac/
U2 - 10.3390/biom15010092
DO - 10.3390/biom15010092
M3 - Article
C2 - 39858486
VL - 15
JO - Biomedicines
JF - Biomedicines
SN - 2227-9059
IS - 1
M1 - 2561
ER -
ID: 62715628